Non-catalytic ketoform syntheses

Abstract

A known base-induced catalytic ketoform synthesis can now be carried out without sacrificing the directivity of the prior art process, but non-catalytically, that is, in the absence of the phase transfer catalyst heretofore required, provided the ketone/araldehyde is present in large excess from about 2 to about 25 times the calculated molar amount necessary to yield the reaction product. This synthesis obviates the problems of separating and recovering a phase transfer catalyst used in the prior art process.

I claim: 
     
       1. A method for introducing an amine substituent into a carbonyl-containing compound comprising, contacting a primary or secondary amine reactant compound which is an amine nucleophilic agent with said carbonyl-containing compound selected from the group consisting of a saturated acyclic monoketone, a saturated cyclic monoketone and, benzaldehyde, optionally substituted with lower alkyl having from 1 to about 6 carbon atoms, in the absence of a phase transfer catalyst and a primary alcohol solvent, and in the presence of a base and sufficient haloform to provide a reaction product selected from the group consisting of a monoazacycloalkanone, diazacycloalkanone, alpha-aminoacetamide, and alpha-amino acetate;   said carbonyl-containing compound being present in an amount from about 2 to about 25 times greater than the molar amount required to react with said reactant compound;   maintaining the temperature during reaction below that which degrades said reactant compound; and,   recovering said reaction product having said amine substituent.   
     
     
       2. The method of claim 1 wherein said base is an alkali metal hydroxide. 
     
     
       3. The method of claim 2 wherein said alkali metal hydroxide is present in a molar amount about three times greater than the molar amount of said reactant compound. 
     
     
       4. The method of claim 1 wherein said acyclic ketone is a lower alkyl ketone having from 2 to about 6 carbon atoms, and said cyclic ketone is a cycloalkanone having from 5 to about 8 ring carbon atoms. 
     
     
       5. The method of claim 1 wherein said primary or secondary amine having from 1 to about 24 carbon atoms wherein functional groups may be substituted with alkyl groups. 
     
     
       6. The method of claim 3 wherein said alkali metal hydroxide is in solid finely divided form. 
     
     
       7. A method for preparing a polysubstituted 2-keto-1,4-diazacycloalkane reaction product from an acyclic or cyclic 1,2-diamine or 1,3-diamine, comprising, contacting said 1,2-diamine or 1,3-diamine with a carbonyl-containing compound selected from the group consisting of a saturated acyclic monoketone, a saturated cyclic monoketone and, benzaldehyde, optionally substituted with lower alkyl having from 1 to about 6 carbon atoms, present in an amount from about 2 to about 25 times greater than the molar amount required to react with said diamine, in the absence of a phase transfer catalyst and a primary alcohol solvent, and in the presence of a base and sufficient haloform to provide said reaction product;   maintaining the temperature of reaction in the range from above about the freezing point of the reaction mass up to about the reflux temperature of said reaction mass; and,   recovering said polysubstituted 2-keto-1,4-diazacycloalkanone.   
     
     
       8. The method of claim 6 wherein said diamine is an N-piperidinyl substituted diamine and said reaction product is a piperidinyl substituted 1,4-diaza-2-cycloalkanone. 
     
     
       9. The method of claim 6 wherein said diamine is a N-substituted-N'-substituted-N-alkanediamine and said reaction product is a polysubstituted piperazinone. 
     
     
       10. A method for preparing a polysubstituted alpha-aminoacetamide reaction product from an amino-piperidine comprising, contacting said amino-piperidine with a carbonyl-containing compound selected from the group consisting of a saturated acyclic monoketone, a saturated cyclic monoketone and, benzaldehyde, optionally substituted with lower alkyl having from 1 to about 6 carbon atoms, present in an amount from about 2 to about 25 times greater than the molar amount required to react with said amino-piperidine, in the absence of a phase transfer catalyst and a primary alcohol solvent, and in the presence of a base and sufficient haloform to provide said reaction product;   maintaining the temperature of reaction in the range from above about the freezing point of the reaction mass up to about the reflux temperature of said reaction mass; and,   recovering said polysubstituted alpha-aminoacetamide.   
     
     
       11. A method for preparing a polysubstituted alkali metal hydroxy-aminoacetate reaction product from an amino-alkanol reactant, comprising, contacting said amino-alkanol with a carbonyl-containing compound selected from the group consisting of a saturated acyclic monoketone, a saturated cyclic monoketone and, benzaldehyde, optionally substituted with lower alkyl having from 1 to about 6 carbon atoms, present in an amount from about 2 to about 25 times greater than the molar amount required to react with said amino-alkanol, in the absence of a phase transfer catalyst and a primary alcohol solvent, and in the presence of a base and sufficient haloform to provide said reaction product;   maintaining the temperature of reaction in the range from above about the freezing point of the reaction mass up to about the reflux temperature of said reaction mass; and,   recovering said polysubstituted alkali metal hydroxy-aminoacetate.